title: Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.
abstract: Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized mainly by progressive cerebellar ataxia, oculocutaneous telangiectasia, and immunodeficiency. This disease is caused by mutations of the ataxia telangiectasia mutated (Atm) gene. More than 500 Atm mutations that are responsible for A-T have been identified so far. However, there have been very few A-T cases reported in China, and only two Chinese A-T patients have undergone Atm gene analysis. In order to systemically investigate A-T in China and map their Atm mutation spectrum, we recruited eight Chinese A-T patients from six unrelated families nationwide. Using direct sequencing of genomic DNA and the multiplex ligation-dependent probe amplification, we identified twelve pathogenic Atm mutations, including one missense, four nonsense, five frameshift, one splicing, and one large genomic deletion. All the Atm mutations we identified were novel, and no homozygous mutation and founder-effect mutation were found. These results suggest that Atm mutations in Chinese populations are diverse and distinct largely from those in other ethnic areas.
authors.affiliation: Department of Medical Genetics, Peking University Health Science Center, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Jianchun
authors.initials: J
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.forename: Rongjun
authors.initials: R
authors.lastname: Xia
authors.forename: Xianhou
authors.initials: X
authors.lastname: Yuan
authors.forename: Mingshan
authors.initials: M
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D001260:Ataxia Telangiectasia / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001284:Atrophy; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002681:China; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D022821:RNA Splice Sites / Q000235:genetics; D017384:Sequence Deletion; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: C097353:AFP protein, human; D018389:Codon, Nonsense; D022821:RNA Splice Sites; D000509:alpha-Fetoproteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins